Animals such as mammals are often susceptible to parasite infestations. These parasites may be ectoparasites, such as insects, and endoparasites such as filariae and worms. Domesticated animals, such as cats and dogs, are often infested with one or more of the following ectoparasites:                fleas (Ctenocephalides felis, Ctenocephalides sp. and the like),        ticks (Rhipicephalus sp., Ixodes sp., Dermacentor sp., Amblyomma sp. and the like),        mites (Demodex sp., Sarcoptes sp., Otodectes sp. and the like),        lice (Trichodectes sp., Cheyletielfa sp., Linognathus sp., and the like), and        flies (Hematobia sp., Musca sp., Stomoxys sp., Dermatobia sp., Cochliomyia sp., mosquitoes (family Culicidae) and the like).        
Fleas are a particular problem because not only do they adversely affect the health of the animal or human, but they also cause a great deal of psychological stress. Moreover, fleas are also vectors of pathogenic agents in animals, such as dog tapeworm (Dipylidium caninum) and may also transmit pathogens to humans.
Similarly, ticks are also harmful to the physical and psychological health of the animal or human. However, the most serious problem associated with ticks is that they are the vector of pathogenic agents, which cause diseases in both humans and animals. Major diseases which are caused by ticks include borreliosis (Lyme disease caused by Borrelia burgdorfen), babesiosis (or piroplasmosis caused by Babesia sp.) and rickettsiosis (also known as Rocky Mountain spotted fever). Ticks also release toxins which cause inflammation or paralysis in the host. Occasionally, these toxins are fatal to the host, such as in the case of the Australian paralysis tick, Ixodes holocyclus. 
Moreover, mites and lice are particularly difficult to combat since there are very few active substances which act on these parasites and they require frequent treatment. Likewise, farm animals are also susceptible to parasite infestations. For example, cattle are affected by a large number of parasites (e.g., arthropod pests, such as fleas, lice and ticks, and mites). A parasite that is very prevalent among farm animals is the tick genus Boophilus. especially those of the species micropJus (cattle tick), decoloratus and anulatus. Ticks, such as Boophilus microplus, are particularly difficult to control because they live in the pasture where the farm animals graze. Other important parasites of cattle and sheep are listed below:                (a) myiases such as Dermatobia hominis (known as Berne in Brazil), Hypoderma, and Cochlyomia hominivorax (greenbottle); sheep myiases such as Lucilia sericata, Lucilia cuprina (known as blowfly strike in Australia, New Zealand and South Africa). These are flies whose larva constitutes the animal parasite;        (b) flies proper, namely those whose adult constitutes the parasite, such as Haematobia irritans (i.e., horn fly);        (c} lice such as Linognathus vitui etc.; and        (d) mites such as Sarcoptes scabiei and Psoroptes ovis. The above list is not exhaustive and other ectoparasites are well known in the art to be harmful to animals.        
Protection of animals against parasites is essential to insure a healthy and safe environment for animals and their owners. Pour-on and spot-on topical formulations are widely used to deliver treatment against variety of external and internal parasiticids, such as ticks, fleas, flies, mites, worms, etc. These formulations are solutions that are applied onto the back of an animal and allowed to spread or penetrate. To be effective, these formulations need to retain an active in upper layers of skin or drive an active into the skin for systemic absorbtion, and to be able to withstand environmental stress (e.g., rain), to prevent removal of the drug. Depending on the intended use, topical formulations typically consist of a solvent with or without a penetration enhancer (for systemically delivered drugs), or a solvent or co-solvents with addition of spreading agent, and various performance additives for delivery into upper layers of the skin. This is a traditional approach to formulating a topical pour-on or spot-on solution. Currently marketed topical pour-ons for production animals for protection from external parasites do not have good water resistance and need to be re-applied frequently.
For example, the commercial products for control of horn fly on cows provide limited protection lasting from several days to two weeks and require re-application after rain throughout the fly season. This creates unnecessary stress for animals resulting in significant productivity losses and additional labor efforts for farmers.
Current commercially available topical solutions to control horn fly population on cows provide limited duration of protection lasting from several days to about two weeks. Current treatments further require frequent re-application due to a wash-off after exposure to environmental conditions such as rain.
Extension of efficacy to one month or longer will provide continuous protection against the horn fly with less frequent applications. Fewer applications will be less stressful for the animals and less time and labor consuming for the farmers.
There are several problems that contribute to the short duration of the active ingredient(s) in the current pour-on nonsystemic formulations. First, the conventional solvent system (organic solvents) applied topically is expected to spread the active ingredient and retain it on the skin for the duration of the desired treatment period. Second, a complete dose intended to last for the duration of the treatment period is applied at one time. Third, conventional solvent systems are not well formulated to resist some weather challenges. The active ingredient is completely exposed to environmental conditions. The solvent carrying the active ingredient is washed off during rain, rendering it non-efficacious. Fourth, the solvent system may not stay on the animal during the treatment process resulting in a non-efficacious treatment.
Compounds that exhibit a degree of activity against a wide range of ectoparasites including arthopods and insects are known in the art. One such class of compounds is the arylpyrazoles which are referred to, for example, in U.S. Pat. Nos. 5,122,530; 5,246,255; 5,576,429; 5,885,607; 6,010,710; 6,083,519; 6,096,329; 6,685,954; EP 0 234 119 and EP 0 295 117 (U.S. Pat. Nos. 5,232,940; 5,547,974; 5,608,077; 5,714,191; 5,916,618 and 6,372,774); EP 0 352 944 (U.S. Pat. No. 4,963,575); EP 0780378 (U.S. Pat. Nos. 5,817,688; 5,922,885; 5,994,386; 6,124,339; 6,180,798 and 6,395,906); EP 0846686 (U.S. Pat. No. 6,069,157); WO 98/28278, WO 08/05489, U.S. Pat. No. 7,759,381 and U.S. Pat. No. 8,445,519. All of the aforementioned patents and patent publications are herein incorporated by reference.
The arylpyrazoles are known to possess excellent activity against insects, such as fleas and ticks. Fipronil is a specific type of 1-N-arylpyrazole that is particularly effective against fleas and ticks and is the active ingredient in Frontline® and Frontline Plus®. Another arylpyrazole, 1-(2-chloro-6-fluoro-4-trifluoromethylphenyl)-4-dichlorofluoro-methylsulfinyl-5-methylpyrazole-3-carbonitrile, has structure and properties similar to fipronil.
Other classes of compounds are also known in the art to be effective parasiticides. Examples include macrocyclic lactones (e.g., avermectins and their derivatives ivermectin, eprinomectin, selamectin, doramectin and abamectin), benzimidazoles (e.g., triclabendazole), levamisole, closantel and development inhibitors such as S-methoprene.
There is a need for a formulation that can be applied as a pour-on or a spot-on formulation but offers higher water resistance and extended duration of efficacy. This will decrease stress to the animals and avoid the labor and costs associated with multiple pour-on applications. It will further avoid labor and costs associated with attaching and retrieving ear tags.